Fibrinogen is an important component in the preparation of fibrin sealant, which is used for preventing leakage of fluids, such as air and/or liquid e.g. blood from tissues. Fibrinogen is converted to fibrin by an enzymatic reaction involving thrombin and factor XIII.
Fibrinogen may be converted to a solid form, for example by lyophilization, prior to storage, in order to reduce protein degradation. A solid fibrinogen preparation has the advantage that it can be stored over a relatively long period of time at a temperature of at least 4° C., such as at room temperature, while retaining its biological activity. For therapeutic use, the solid fibrinogen is typically dissolved in an aqueous solvent prior to use. Solutions with high fibrinogen concentration are often required, e.g. when using the fibrinogen as a component of fibrin sealants together with a thrombin component, since typically adhesive strength is proportional to the fibrinogen concentration.
Fibrinogen is among the least soluble of the plasma proteins (The Preparation and Properties of Human Fibrinogen of Relatively High Solubility*M. W. Mosesson, Sol Sherry Biochemistry, 1966, 5 (9), pp 2829-2835). Thus, it is difficult and time consuming to dissolve a solid fibrinogen preparation to obtain a solution with high fibrinogen concentration e.g. at least 40 mg fibrinogen/ml. The problem is further complicated when foam forms and disappears slowly during dissolution of the solid fibrinogen composition. The presence of foam can further prolong the dissolution time and/or negatively affect the fibrinogen functionality, and the mechanical properties of the fibrin sealant prepared with the fibrinogen solution.
Background art includes U.S. Pat. Nos. 6,349,850; 4,650,678; 4,909,251; and 5,962,405; U.S. Patent Publication No. 2004/0005310; and European Patent Publication No. EP 2130549A1.
There is an unmet need for a method and a device enabling fast dissolution of solid fibrinogen to form a high concentrated fibrinogen solution without the addition of excipients to increase the solubility of fibrinogen.